A new study published online today by JAMA shows that among patients age 65 years and older, rosiglitazone (a medication for treating Type 2 diabetes) is associated with an increased risk of stroke, heart failure, and all-cause mortality (death) when compared with pioglitazone (another medication for diabetes). The study was published online today in advance of an upcoming Food and Drug Administration meeting that will review the safety of rosiglitazone. The paper will appear in the July 28 print issue of JAMA.

"Rosiglitazone and pioglitazone are the only thiazolidinediones (a class of drugs for treating diabetes) currently marketed in the United States," the authors provide as background information. "Studies have suggested that the use of rosiglitazone may be associated with an increased risk of serious cardiovascular events compared with other treatments for type 2 diabetes."

David J. Graham, M.D., M.P.H., from the Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, MD and colleagues, evaluated data from 227,571 Medicare beneficiaries (average age, 74.4 years) who started treatment with rosiglitazone or pioglitazone through a Medicare Part D prescription drug plan from July 2006 through June 2009. The patients were followed for up to three years after the initiation of the medications.

"During follow-up, there were 1,746 acute myocardial infarctions [heart attacks] (21.7 percent fatal), 1,052 strokes (7.3 percent fatal), 3,307 hospitalizations for heart failure (2.6 percent fatal), and 2,562 deaths for all causes among cohort members," the authors report. Analysis showed no differences in the risk for heart attack between rosiglitazone and pioglitazone, but "...our study found that rosiglitazone was associated with a 1.25-fold increase in risk of heart failure compared with pioglitazone," and "...these data suggest that rosiglitazone was associated with a 1.27-fold increased risk of stroke and a 1.14-fold increased risk of death compared with pioglitazone," according to the authors.

In conclusion, the authors write: "...in a population of more than 227,000 patients 65 years or older who initiated treatment with a thiazolidinedione, we found that, compared with pioglitazone, rosiglitazone was associated with an increased risk of stroke, heart failure, and death and the composite of AMI (heart attack), stroke, heart failure or death."
(JAMA.doi:10.1001/jama.2010.920. Available to the media pre-embargo at www.jamamedia.org.)

Editor's Note: This study was funded by the Office of the Assistant Secretary for Planning and Evaluation (ASPE), the Centers for Medicare & Medicaid Services (CMS), and the U.S. Food and Drug Administration (FDA). Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Rosiglitazone and the Case for Safety Over Certainty

In an accompanying editorial, David Juurlink, M.D., Ph.D., of the Sunnybrook Research Institute; the Departments of Medicine, Pediatrics and Health Policy, Management, and Evaluation at the University of Toronto; and the Institute for Clinical Evaluative Sciences, Toronto, highlights the importance of the findings of the report by Graham and colleagues in terms of understanding the risks of rosiglitazone.

Dr. Juurlink writes, "The epilogue of the rosiglitazone story has yet to be written, but a few observations can now be made with confidence. First, there is no direct evidence that rosiglitazone prevents vascular events in patients with diabetes. Second, converging lines of evidence suggest that rosiglitazone is less safe than pioglitazone, whereas no data suggest that the converse might be true. Third, because the evidence to date is not conclusive, differing views have emerged on how to proceed in the face of uncertainty. ... Whether rosiglitazone and pioglitazone really do have different cardiovascular safety profiles is an intriguing question but one with a misplaced focus. Accumulating concerns about rosiglitazone make it difficult to advance a cogent argument why, exactly, a patient might want to receive the drug or why a physician would choose to prescribe it when there is an available and quite possibly safer alternative."
(JAMA.doi:10.1001/jama.2010.954. Available to the media pre-embargo at www.jamamedia.org)

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